In addition to the FDA-approved definition of a circulating tumor cell (CTC), various CTC phenotypes have been discovered. Epithelial-mesenchymal transition (EMT) of cancer cells is directly linked to PD-L1 upregulation. The goal of the study was to investigate PD-L1 expression and EMT in CTCs of non-small cell lung cancer (NSCLC) patients, and perform an outcome analysis. Prospectively, 7.5 mL peripheral blood was collected from 30 NSCLC patients that underwent surgery and 15 healthy controls. CTCs were enriched by size-based microfilter and immunofluorescence stainings performed (cytokeratin (CK) 8/18/19, EpCAM, CD45, PD-L1, EMT markers vimentin, and N-Cadherin, DAPI). Patient-matched NSCLC tissues were also stained. CTC staining intensity was quantified with a software and correlated with patient-matched NSCLC tissues and survival. PD-L1 and EMT markers were expressed at significantly higher proportions in CTCs than patient-matched NSCLC tissues (p < 0.05); ≥3 PD-L1pos/EMTposCTCs were associated with significantly poorer survival after curative surgery (p < 0.05). No CTCs were detected in 15 healthy controls. This study shows that PD-L1 expression and EMT of CTCs is a negative survival predictor for NSCLC patients. The therapeutic role of the molecular linkage of PD-L1 and EMT will need to be further investigated, as linked pathways could be targeted to improve NSCLC outcome.
More than half of young adults at risk for alcohol-related harm report symptoms of insomnia. Insomnia symptoms, in turn, have been associated with alcohol-related problems. Yet one of the first-line treatments for insomnia (Cognitive Behavioral Therapy for Insomnia or CBT-I) has not been tested among individuals who are actively drinking. This study tested (1) the feasibility and short-term efficacy of CBT-I among binge-drinking young adults with insomnia and (2) improvement in insomnia as a predictor of improvement in alcohol use outcomes. Young adults (ages 18–30 years, 75% female, 73% college students) who met criteria for Insomnia Disorder and reported 1+ binge drinking episode (4/5+ drinks for women/men) in the past month were randomly assigned to 5 weekly sessions of CBT-I (n = 28) or single-session sleep hygiene (SH, n = 28). All participants wore wrist actigraphy and completed daily sleep surveys for 7+ days at baseline, posttreatment, and 1-month follow-up. Of those randomized, 43 (77%) completed posttreatment (19 CBT-I, 24 SH) and 48 (86%) completed 1-month follow-up (23 CBT-I, 25 SH). CBT-I participants reported greater posttreatment decreases in insomnia severity than those in SH (56% vs. 32% reduction in symptoms). CBT-I did not have a direct effect on alcohol use outcomes; however, mediation models indicated that CBT-I influenced change in alcohol-related consequences indirectly through its influence on posttreatment insomnia severity. CBT-I is a viable intervention among individuals who are actively drinking. Research examining improvement in insomnia as a mechanism for improvement in alcohol-related consequences is warranted. U.S. National Library of Medicine, https://clinicaltrials.gov/ct2/show/NCT03627832, registration #NCT03627832
1 June 2017 in American Journal of Preventive Medicine